19-8321670-GG-TT

Position:

• chr19-8321670-GG-TT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001031.5(RPS28):​c.54_55delGGinsTT​(p.Gly19Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS28 NM_001031.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.06

Genes affected

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS28	NM_001031.5	c.54_55delGGinsTT	p.Gly19Cys	missense_variant		ENST00000600659.3	NP_001022.1
RPS28	XM_047439201.1	c.54_55delGGinsTT	p.Gly19Cys	missense_variant			XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS28	ENST00000600659.3	c.54_55delGGinsTT	p.Gly19Cys	missense_variant		1	NM_001031.5	ENSP00000472469.1
RPS28	ENST00000602140.1	n.90_91delGGinsTT		non_coding_transcript_exon_variant	2/2	1
RPS28	ENST00000417088.2	n.37_38delGGinsTT		non_coding_transcript_exon_variant	1/3	2
RPS28	ENST00000449223.3	n.427_428delGGinsTT		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 21, 2024

This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 19 of the RPS28 protein (p.Gly19Cys). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with RPS28-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-8386554;